The study of neuronal activity in awake, freely moving animals is the most representative view of `normal'neuronal function. Anesthetics and restraint have profound effects on neuronal physiology and the correlate animal behavior. The study of real time neuronal event processing requires recording methods with high temporal bandwidth (>500 kHz) and the ability to detect physiologically relevant events (i.e. voltage changes or calcium flux). Currently only microelectrode recording of single neuronal units, multiunit activity and field potentials have sufficient temporal resolution and portability to allow recording of neuronal activity in freely moving animals. The current project will produce a miniature microscope/imaging chip which can be head mounted and will allow the recording of optical signals of changes in membrane voltage and calcium concentration in neurons in freely moving rodents. We have developed a prototype device that can collect wide field image sequences of fluorescent voltage dye signals. The current application will re-engineer and significantly improve this prototype device. We will systematically engineer each component to maximize excitation light delivery, fluorescent light collection and optical resolution while minimizing weight, volume, and heat generation. The device will be capable of recording rapid (1 kHz) fluorescent image sequences of a 2-3 mm2 area of cortex and detect small changes in F/F (0.1%). The device will contain a custom designed and built excitation light source, dichroic excitation and emission filters, dichroic mirror, collector lens, objective lens and imaging chip. The device will be small (<1.8 cm2) and light weight enough (10g) to be mounted on the head of a freely moving rat and possibly a mouse. The device will be developed and validated in studies of i) barrel cortex activity during active whisking and object discrimination as well as ii) olfactory bulb activity during active sniffing and scent recognition. The device is intended as a precursor to devices that can translate neuronal activity into actions in real time (optical brain machine interface). PUBLIC HEALTH RELEVANCE: This project will develop a device to study brain function in awake, behaving mammals. The device represents the first step in the development of a neuroprosthetic device to capture information from neuronal tissue regarding intended function. Such a device can ultimately be used to allow direct brain control of robotics, computers and instrumentation to allow paralyzed patients a way to exert conscience control of their environment.